期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1866, 期 5, 页码 819-827出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2019.02.008
关键词
BAG3; ISG15; Ago2; Pancreatic cancer; Cancer stem cell
资金
- National Natural Science Foundation of China [81572828, 81602510, 81602439]
- China Postdoctoral Science Foundation [2017M611286]
BAG3 is a member of the cochaperone BAG family and often highly expressed in various cancers. Recently, evidences show that BAG3 promotes sternness of human cancer cells. IFN-stimulated genes 15 (ISG15) is an ubiquitin-like molecule, which is covalently conjugated with substrates to form ISGylated proteins. Global screening BAG3 interacting partners demonstrated that ISG15 might be a potential binding partner. The current study revealed that BAG3 did not interact with ISG15, but positively regulated ISG15 expression in pancreatic ductal adenocarcinoma cancer (PDAC). It was further found that BAG3 deletion stabilized ISG15 mRNAs, while suppressed its translation via increasing Serine phosphorylation of Ago2 at position 387 (S387). Both BAG3 deletion and ISG15 knockdown suppressed stem cell-like phenotypes of PDAC cells, including clonogenicity, invasiveness and spheroid formation. In addition, ectopic ISG15 expression rescued the suppressive role of BAG3 deletion in cancer stern cell (CSC)-like phenotypes of PDAC cells, and this effect of ISG15 was independent of its ISGylation function. The current study implies that BAG3 and ISG15 may provide a therapeutic advantage for PDAC.
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